Current Opinion in Hematology最新文献

Purpose of review: 10-20% of myeloproliferative neoplasms (MPNs) are diagnosed in adolescent and young adult (AYA) patients. This review aims to summarize current literature on AYA MPN, to highlight unique clinico-pathological patterns, specific treatment paradigms and areas for further research.

Recent findings: Epidemiological data highlights the female predominance in AYA MPN, reflective of the higher burden of essential thrombocythemia (ET) within this population. Fatigue is common and can be severe but is frequently overlooked within the healthcare setting. Compared to older MPN, cytopenias are less common and CALR mutations are frequently encountered. Interferon is the preferred first-line agent in AYA MPN and holds potential for disease modification. Clinicians should be mindful of the unique challenges facing AYA patients including professional demands, family planning, pregnancy and psychological health when assessing and counselling patients with MPN.

Summary: AYA MPN patients have unique clinico-pathological characteristics that alter their disease presentation, thrombo-haemorrhagic risks and kinetics of progression. Further research should focus on developing AYA-specific risk stratification models, the impact of nondriver somatic mutations, and therapies with potential for disease modification.

Purpose of review: TP53- mutated ( TP53 -MT) myeloid neoplasms (MN) represent one of the most challenging disease subsets due to their distinct pathobiology, frequent association with therapy-related disease, chemo-resistant phenotype, and dismal outcomes. The prognostic impact of TP53 -MT is not uniform and is influenced by disease state, allelic burden, and co-occurring cytogenetic and molecular aberrations that shape disease trajectory. While current prognostic models incorporate TP53 status, they incompletely capture the heterogeneity within TP53 -MT MN. Therapeutic options remain limited, with allogeneic stem cell transplantation being the only intervention offering long-term survival in selected patients.

Recent findings: Novel approaches, including p53 reactivators and anti-CD47 antibodies in combination with standard-of-care therapies, have been explored; however, none has yet transformed the natural history of TP53 -MT MN.

Summary: This review highlights the current understanding of TP53 -MT MN, evolving strategies of prognostic stratification and propose a practical framework for clinical management. We further discuss the critical unmet need for collaborative, biologically informed clinical trials to improve outcomes of this challenging disease entity.

Purpose of review: Myeloproliferative neoplasm-unclassifiable (MPN-U) is a heterogenous subtype of Philadelphia-chromosome negative (Ph-) MPN that comprises 5-20% of Ph- MPN cases. Given the clinical and molecular variability of presentation, there are no clear data regarding risk stratification and management of MPN-U. In this review, we aim to summarize the current evidence regarding MPN-U with regards to diagnosis, risk stratification, and treatment approaches.

Recent findings: Current diagnostic criteria require exclusion of other chronic myeloid malignancies along with identifying the typical pathologic findings of an MPN in order to diagnose MPN-U. While there are not dedicated prognostic scores regarding thrombotic risk and survival specifically for MPN-U, phenotype-agnostic scores may have utility. In addition, the Dynamic International Prognostic Scoring System (DIPSS)+ score has demonstrated that it can identify higher-risk MPN-U. There are no consensus treatment recommendations available for MPN-U.

Summary: When considering management of MPN-U, for patients in the cellular phase, we consider cytoreduction in patients identified as high-risk, for fibrotic-phase disease, we consider JAK inhibition for splenomegaly/constitutional symptoms and allogeneic transplantation for higher-risk patients, and for accelerated/blast-phase disease we employ hypomethylating-agent based approaches with the intent of allogeneic transplant for eligible patients.

Purpose of review: Advances in proteomics continue to expand our understanding of how protein systems regulate platelet function in hemostasis, thrombosis, and inflammation. However, clinical translation of platelet proteomics findings remains limited. This review highlights recent studies of platelet proteomes and platelet function in development, aging, and disease.

Recent findings: Studies have defined platelet proteomes associated with hypoactivity and hyperactivity across embryonic, neonatal, adult, and aging states. Phosphoproteomics has revealed signaling pathways linked to platelet dysregulation in aging, nutrient states, and specific diseases. Analyses of platelet secretomes and extracellular vesicles show agonist, therapy, and disease-associated signatures in diabetes, neurodegeneration, cancer, and myeloproliferative neoplasms. Proteomic profiling of thrombi in myocardial infarction, stroke, and sepsis has uncovered distinct signatures implicating platelets in clot architecture, fibrinolysis resistance, and immune crosstalk.

Summary: Proteomics continues to define alterations in platelet composition shaped by development, aging, and disease, identifying molecular effectors of platelet function and pointing to biomarkers and therapeutic targets. Platelet proteomics is increasingly positioned to inform precision strategies in thrombotic and inflammatory disorders and to refine models of vascular biology and medicine.

Purpose of review: Optimized platelet isolation is essential for preserving platelet integrity and function. This review elucidates the scientific rationale behind common workflows, explores modern strategies for their refinement, and aims to improve practices in translational hematology.

Recent findings: Recent research has increasingly highlighted the multifaceted roles of platelets beyond their traditional function in hemostasis, underscoring the necessity for precise and reliable isolation techniques. Inadequate or improper isolation methods can inadvertently trigger platelet activation. Although a wide array of isolation protocols exists, their selection is often based on empirical convention rather than scientifically validated criteria. This review provides a critical evaluation of commonly employed platelet isolation methods, examining their advantages, limitations, and the challenges they pose, particularly with respect to minimizing unintended platelet activation. In addition, we discuss innovative approaches that aim to overcome these limitations, including the application of supramolecular anticoagulants. Finally, we explore the transformative potential of artificial intelligence driven technologies to optimize or even replace conventional platelet isolation techniques.

Summary: This review analyzes established platelet isolation protocols, clarifying their rationale and key overlooked factors. It explores the potential of emerging technologies, particularly artificial intelligence, to transform platelet research, raising the question of whether these advancements could replace traditional methods.

Purpose of review: This review aims to provide an updated overview of platelet concentrates, particularly platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), and their evolving applications in periodontal therapy. It highlights their regenerative potential, mechanisms of action, and clinical outcomes in managing periodontal defects.

Recent findings: Recent findings emphasize PRF's superiority over PRP due to its simpler preparation, sustained release of growth factors, and absence of anticoagulants, promoting enhanced tissue healing and bone regeneration. Studies support the adjunctive use of PRF in procedures like flap surgeries, intrabony defect treatment, and gingival recession coverage. Clinical evidence favors PRF as a predictable, biocompatible aid in modern periodontal regenerative strategies.

Summary: Its unique three-dimensional fibrin network supports cellular migration and acts as a framework for tissue regeneration, offering gradual release of growth factors like transforming growth factor-beta and platelet-derived growth factor. Advanced forms, such as injectable PRF, are developed to enhance clinical outcomes by promoting fibroblast migration and tissue regeneration. This review explores the various types of platelet concentrates, their preparation methods, and their applications in periodontal therapy. It highlights the potential of PRF in enhancing periodontal regeneration, offering a comprehensive overview of current advancements and future directions in this field.

Purpose of review: Primary immune thrombocytopenia (ITP), an immune-mediated hemorrhagic disease, features an intricate pathogenesis that involves megakaryocyte malfunction and hyperresponsiveness of the innate and adaptive immune systems. As a second-line drug for ITP, rituximab acts quickly and can produce an initial response rate of up to 60%. However, this response only lasts for a short term, meanwhile challenged by resistance, relapse and side effects. Additionally, no reliable clinical parameters have been proposed for forecasting the therapeutic response of patients. Furthermore, the application of rituximab is restricted in specific populations, including pregnant patients, children with positive antithyroid antibodies, and patients contaminated with HBV.

Recent findings: Splenectomy and new drugs that target the thrombopoietin receptor, FcγR, FcRn, B-cells or plasma cells, T-cells, and complement pathways may overcome these shortcomings.

Summary: This article summarizes the barriers limiting the use of rituximab, and discusses the effectiveness and safety of current and fledgling treatment options.